The risk of risk of upper gastrointestinal bleeding (UGIB) among NSAID users (traditional NSAIDs and coxibs) has been evaluated in a systematic review of observational studies published between 2000 and 2008.
The review included 18 original studies initially, 9 of which were excluded for a number of reasons, leaving 9 for the meta-analysis. The following findings were reported:
• The relative risk (RR) of UGIB for traditional NSAIDs was 4.50 (3.82 to 5.31) and for coxibs 1.88 (0.96 to 3.71).
• Lower RRs than that reported overall were observed for ibuprofen 2.6 (2.17 to 3.33), rofecoxib 2.12 (1.5 to 2.84), aceclofenac 1.44 (0.65 to 3.2) and celecoxib 1.42 (0.85 to 2.37).
• Higher RRs than that reported overall were observed for ketorolac 14.54 (5.87 to 36.04) and piroxicam 9.94 (5.99 to 16.50).
• Estimates of RR were 5.63 (3.83 to 8.28) for naproxen, 5.57 (3.94 to 7.87) for ketoprofen, 5.40(4.16 to 7.00) for indomethacin, 4.15(2.59 to 6.64) for meloxicam and 3.98(3.36 to 4.72) for diclofenac.
• The degree of inhibition of whole blood COX-1 did not significantly correlate with RR of UGIB associated with individual NSAIDs (p=0.058) but a profound and coincident inhibition (> 80%) of both COX-isozymes was associated with higher risk.
• NSAIDs with long plasma half-life and with a slow-release formulation were associated with a greater risk than NSAIDs with a short half-life.
The researchers noted that previous overviews of epidemiological studies published in the 1990’s consistently showed that use of tNSAIDs was associated with around a 4-fold increased risk of UGIB and a clear dose dependent elevation in risk. They note that their meta-analysis has added the cumulative evidence published since 2000 confirming this magnitude of increased risk for traditional NSAIDs as well as the dose-response relationship, and provided the summary estimate of UGIB for coxibs that are associated with an approximate two-fold increased risk. They conclude “the risk of UGIB varied between individual NSAIDs at the doses commonly used in the general population. Drugs with long half-life or slow-release formulation and/or associated with profound and coincident inhibition of both COX-isozymes were associated with a greater risk of UGIB.” They acknowledge that the findings from these epidemiological studies are open to some residual confounding.”